Advance Publication

Journal of Atherosclerosis and Thrombosis

Accepted for publication: October 6, 2009
Journal of Atherosclerosis and Thrombosis  Vol.17, No. 4 1
published online: February 3, 2010
Review

Adipose Tissue, Inflammation and Atherosclerosis

Birgit Gustafson

The Lundberg Laboratory for Diabetes Research, Center of Excellence for Metabolic and Cardiovascular Research, Department of
Molecular and Clinical Medicine, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

Metabolic syndrome is associated with dysfunctional adipose tissue that is most likely a consequence
of the enlargement of adipocytes and infiltration of macrophages into adipose tissue. Obesity and
ectopic lipid deposition are major risk factors for diseases ranging from insulin resistance to type 2
diabetes and atherosclerosis. Enlargement of adipocytes, due to impaired adipocyte differentiation,
leads to a chronic state of inflammation in the adipocytes and adipose tissue with a reduction in the
secretion of adiponectin and increase in the secretion of proinflammatory cytokines such as interleu-
kin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1. The secretion of cytokines like
tumour necrosis factor (TNF)-α, mainly from macrophages, enhances local inflammation. These
proinflammatory cytokines might also substantially affect cardiovascular function and morphology.
Furthermore, a proinflammatory state in adipose tissue can lead to local insulin resistance with an
impaired inhibitory effect of insulin on the release of FFAs and endothelial dysfunction that clearly
promotes cardiovascular diseases and type 2 diabetes. The underlying mechanisms of ectopic fat
accumulation in various tissues and the impact on metabolic syndrome and its association with insu-
lin resistance are discussed.

J Atheroscler Thromb, 2010; 17:000-000.

Key words; Obesity, Insulin resistance, Cytokines, Vascular injury

tissue biology and endocrine function. Obesity, char-

Introduction
For many years, adipose tissue was regarded
merely as a heat insulator and a store of excess free
fatty acids (FFAs) that could be released when needed.
However, following the identification of adipokines,
adipose tissue is now recognized to play a central role
in the pathophysiology of insulin resistance and meta-
bolic syndrome 1). Waist circumference, an easy-to-
measure marker of metabolic risk and used to define
metabolic syndrome, has been shown to correlate with
different components of the syndrome supporting the
notion that visceral obesity plays an important role in
the development of cardiovascular diseases as well as
insulin resistance and type 2 diabetes. Several recent
studies have increased the understanding of adipose
Address for correspondence: Birgit Gustafson, Department of
Molecular and Clinical Medicine, Sahlgrenska University
Hospital, Blå Stråket 3, 413 45 Göteborg, Sweden
E-mail: birgit@medic.gu.se
Received: September 15, 2009
Accepted for publication: October 6, 2009
acterized by enlarged adipocytes, and insulin resistance
are associated with impaired adipogenesis and a low-
grade chronic inflammation that to a large extent
emanates from adipose tissue 2). The secretion of bio-
active molecules from adipose tissue might have an
effect on insulin sensitivity in the liver and peripheral
tissues, and have a negative impact on the cardiovas-
cular system. In this review, current knowledge of low-
grade chronic inflammation in adipose tissue with
local and systemic effects will be discussed.
Adipose Tissue
Adipose tissue in mammals can be divided into
white and brown adipose tissue (WAT and BAT).
WAT is not homogenous, and can be divided into
subcutaneous and visceral adipose tissue. Subcutane-
ous adipose tissue stores excess calories and can be fur-
ther divided into upper and lower body obesity, while
visceral adipose tissue (omental and mesenteric) sup-
plies the inner organs with energy. There is 3 to 4

2 Gustafson
Fig. 1. Cross-talk between adipose tissue and other organs.
Adipose tissue is a key endocrine organ that releases several adipo-
kines capable of affecting other tissues and playing an important
role in the pathophysiology of insulin resistance and metabolic
syndrome.
times more subcutaneous than visceral adipose tis-
sue 3), and it appears that these two tissue types can
interact in a coordinated and compensatory manner 4).
Although WAT and BAT share many metabolic
characteristics, WAT stores energy whereas BAT dissi-
pates energy. The role of BAT in adult humans is
unclear but it has been recently proposed that it can
be induced to increase glucose uptake 5). Furthermore,
genes characteristic of human BAT have been shown
to negatively correlate with obesity and insulin sensi-
tivity 6, 7).
Adipose Tissue as an Endocrine Organ
Adipose tissue is a key endocrine organ with
autocrine regulation. It has a central role in obesity-
associated complications such as dyslipidemia, insulin
resistance and type 2 diabetes as well as low-grade
inflammation and increased risk of cardiovascular dis-
ease and metabolic syndrome 8). It is now established
that adipose tissue comprises ~50% adipocytes and
~50% other cells including preadipocytes, vascular,
neural and immune cells and leucocytes 9). The adipo-
cytes, preadipocytes and macrophages within adipose
tissue secrete a wide range of hormones and cytokines,
including interleukin (IL)-6, IL-8, IL-1β and mono-
cyte chemoattractant protein (MCP)-1 2). It is now
evident that many of these adipokines have the ability
to influence other tissues such as the liver and muscle.
Furthermore, the adipokine leptin affects appetite reg-
ulation, and others have an important impact on
inflammation and vascular biology (Fig. 1).
Advance Publication
Journal of Atherosclerosis and Thrombosis
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published online: February 3, 2010
Fig. 2. Enlargement of adipocytes causes alterations in secre-
tion of adipokines.
Under normal conditions, the adipocyte is a site of lipid synthesis,
uptake and storage. Secreted adipokines function as either endo-
crine, paracrine or autocrine mediators. Increases in adipocyte size
can lead to deleterious alterations in insulin sensitivity caused by a
decrease in adiponectin secretion, an increase in the release of FFAs
and the induction of inflammatory mediators.
The Adipocyte
The adipocyte is a very complex cell. Under nor-
mal conditions, it is involved in lipid synthesis, stor-
age and secretion of anti-inflammatory molecules, but
it can also be induced to secrete a number of inflam-
matory factors such as MCP-1 and IL-6. By acting as
transmitters of endocrine or paracrine signals, the
secreted adipokines can promote either inflammation
or altered insulin sensitivity of the adipocyte (Fig. 2).
Fat mass is dependent on both adipocyte cell
number and size. The number of adipocytes is deter-
mined during early adulthood and changes in fat mass
are attributed to changes in adipocyte cell size 10). The
adipocyte turnover rate in humans was recently estab-
lished to be ~10% per year 10).
Fat cell mass increases with increasing body fat to
a maximum of ~0.7−0.8 μg lipids per cell, and there-
after there is a more rapid increase in fat cell num-
ber 11). In subjects with obesity, adipose tissue has a
lower capacity for the recruitment of new adipo-
cytes 12). Tschoukalova et al. found that the number of
committed preadipocytes was decreased in patients
with obesity independent of fat location 13). In a
recently published study from our laboratory, we
found that the number of mesenchymal precursor
cells was increased in obese individuals but differentia-
tion of preadipocytes into adipocytes was decreased,
suggesting an impaired differentiation of preadipo-
cytes in obesity 2). Therefore, it appears that most adult-
onset obesity is related to the hypertrophy of adipo-
cytes, and enlarged adipocytes is the best obesity-fac-

Adipose Tissue and Atherosclerosis
Fig. 3. Features of metabolic syndrome.
Metabolic syndrome refers to several known risk factors including
insulin resistance, obesity, dyslipidemia and hypertension. The
conditions are interrelated and share underlying mediators. Indi-
viduals who have the same underlying malfunctions are at high
risk of developing type 2 diabetes and cardiovascular disease.
tor in correlation with insulin resistance compared
with other factors related to obesity 1, 14).
Large adipocytes are more insulin-resistant and
lipolytic, and release more inflammatory cytokines
and less adiponectin (Fig. 2) 15). They are also more
frequently found in individuals with obesity-related
metabolic disorders 11). Thus, the relative number of
large adipocytes might be the most important deter-
minant of metabolic activity and the response to envi-
ronmental changes.
Features of Metabolic Syndrome
The term “metabolic syndrome” includes hyper-
tension, dyslipidemia, glucose intolerance and insulin
resistance, variables that all are associated with obe-
sity 16). Dysfunctional adipose tissue with low-grade,
chronic and systemic inflammation links the meta-
bolic and vascular pathogenesis including dyslipid-
emia, low-grade inflammation and insulin resistance
and is a hallmark of disorders such as type 2 diabetes
and cardiovascular disease (Fig. 3). However, lifestyle
factors and, to a lesser degree, genetic factors, are also
involved 17).
Visceral and Subcutaneous Adipose Tissue
A high level of visceral fat is an independent risk
factor for glucose intolerance, insulin resistance, and
cardiovascular disease. Visceral fat refers to the intra-
peritoneal fat composed of the greater and lesser
omentum and mesenteric adipose tissue. Visceral fat
accounts for ~20% of total body fat in men compared
Advance Publication
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Accepted for publication: October 6, 2009
3
published online: February 3, 2010
with only ~6% in pre-menopausal women. A male
risk profile has been characterized in women with
abdominal obesity 11). Enlarged adipocytes in the vis-
cera are characterized by an increased lipolytic state
and are resistant to the anti-lipolytic effects of insu-
lin 18).
Waist circumference is an index of the body’s
periarterial and periarteriolar fat. It is an easy-to-mea-
sure marker of metabolic risk and is used to identify
individuals with metabolic syndrome. However, the
adverse and contributing effects of abdominal subcu-
taneous fat should not be overlooked as up to 80% of
total adipose tissue can be composed of subcutaneous
fat 19).
Visceral and subcutaneous adipose tissue deposits
have constitutive biological differences that are charac-
teristic of their physiological roles. Even though both
deposits serve as energy reservoirs to maintain sys-
temic equilibrium, there are differences in levels of
lipid mobilization, adipokine production and adipo-
cyte differentiation that might be of importance in
responses to diet and exercise 20). Visceral fat secretes
higher levels of complement factors, adiponectin, and
inflammatory markers such as IL-6, IL-8, angioten-
sinogen and plasminogen activator inhibitor-1 4, 21, 22).
Rates of FFA lipolysis are approximately 50%
greater in obese individuals than in healthy subjects,
and higher in subjects with upper body obesity than
those with lower body obesity. However, abdominal
subcutaneous fat is probably the main source of
increased levels of circulating FFA 20). The altered FFA
metabolism and endocrine function in visseral obese
individuals imply that visceral adipose tissue is involved
in the pathophysiology of metabolic syndrome but
this does not exclude a contribution from subcutane-
ous adipose tissue.
TNFα and IL-6
Several studies suggest that tumour necrosis fac-
tor (TNF)α and IL-6 are both involved in obesity-
related insulin resistance and that TNFα is one of the
most important mediators of inflammation 23). In con-
trast to IL-6, TNFα is secreted not by adipocytes but
instead by infiltrating macrophages in adipose tissue,
and functions as a paracrine and/or autocrine fac-
tor 24, 25). It has been shown that adipose tissue is a sig-
nificant source of circulating IL-6 and also related to
BMI and adipocyte size 15). TNFα and IL-6 are known
to promote lipolysis and the secretion of FFA, which
contribute to an increase in hepatic glucose produc-
tion and insulin resistance 26). Both cytokines impair
adipocyte differentiation and instead promote inflam-

4 Gustafson
mation 27). Furthermore, IL-6 promotes inflammation
not only in adipose tissue but in endothelial cells and
liver cells 28). IL-6 also promotes insulin resistance by
interfering with the insulin signaling in adipose tis-
sue 29).
In a recent study in obese individuals, adipokine
levels in the radial artery were compared with those in
the portal circulation to evaluate the possibility that
visceral fat supports systemic inflammation by secret-
ing inflammatory cytokines into the portal circulation
that drains visceral fat 22). The authors found a 50%
increase in the secretion of IL-6 into the portal vein,
but no other differences among the inflammatory
adipokines tested. They also found a direct correla-
tion between the concentrations of IL-6 and systemic
C-reactive protein (CRP) in the portal vein. These
findings indicate that visceral fat is an important site
for IL-6 secretion and provide a potential link between
visceral fat and systemic inflammation in individuals
with abdominal obesity 22).
A further study in overweight men showed that
circulating levels of IL-6 were associated with visceral
adiposity, whereas TNFα showed an association with
overall obesity 30). These results support the hypothesis
that IL-6 mediates the hyperinsulinemic state related
to excess visceral fat while TNFα seems to contribute
to the insulin resistance of overall obesity 30).
Ectopic Fat Accumulation
Ectopic fat is defined as the deposition of triglyc-
erides within cells of non-adipose tissue that normally
contain only small amounts of fat. A positive energy
balance produces a pattern similar to lipodystrophy
with the accumulation of excess lipids in the liver,
skeletal muscle and pancreas indicating that adipose
tissue is not capable of sequestering nutritional lipids
away from these organs 31). The accumulation of fat in
skeletal muscle and viscera is associated with insulin
resistance and cardiovascular disease.
Lipid accumulation in liver and muscle is an
early hallmark of type 2 diabetes. In the pancreas,
lipid accumulation has been shown to precede sup-
pressed glucose-mediated insulin production 32). In the
lipid-overloaded heart, metabolic dysregulation may
induce insulin resistance resulting in impaired glucose
oxidation and, ultimately, heart failure 33). The accu-
mulation of ectopic fat is now considered part of met-
abolic syndrome. However, although the evidence for
its deleterious effects is strong, whether ectopic lipid
accumulation precedes or succeeds insulin resistance is
not clear.
Advance Publication
Journal of Atherosclerosis and Thrombosis
Accepted for publication: October 6, 2009
published online: February 3, 2010
Epicardial Adipose Tissue
Epicardial adipose tissue is metabolically active
and a source of FFA and several bioactive adipokines
such as adiponectin, TNFα, IL-1, IL-6, neural growth
factor and resistin 34, 35). Some of these factors might
substantially affect cardiovascular function and mor-
phology and, thereby, directly contribute to the devel-
opment of the cardiovascular complications of
increased adiposity as well as insulin resistance 34, 35).
Epicardial fat reflects cardiac and visceral adiposity
and is related to intima-media thickness, an increase
in vascular stiffness, and inflammation which plays
a major part in disease progression 36, 37). Individuals
with coronary artery disease show increased macro-
phage infiltration into epicardial fat, suggesting a state
of chronic inflammation 38).
Epicardial adipose tissue may also affect the coro-
nary arteries and myocardium through paracrine
and/or direct secretion of pro-inflammatory adipo-
kines. Epicardial fat has a higher rate of FFA and tria-
cylglycerol uptake than subcutaneous fat, but also a
higher rate of fatty acid breakdown 39).
Perivascular Fat
Perivascular adipose tissue (PAT) surrounds
blood vessels in changing amounts and is produced
from the vascular lamina adventitia in response to
circulating factors and local stimuli 40). PAT has been
considered largely a passive structural support for
arteries. However, it can play an active role in regulat-
ing vascular tone and releases adipocytederived vascu-
lar relaxation factors into blood vessels 41). Excess calo-
ries and inactivity enlarge PAT depots with potentially
unfavorable consequences and an increase in PAT is
suggested to mediate morphologic changes associated
with an increase in vascular stiffness seen in obesity 42).
Insulin Resistance
Large adipocytes are more frequently found in
subjects with impaired glucose tolerance and type 2
diabetes than those with a similar degree of adiposity
but with normal glucose tolerance, and impaired adi-
pocyte differentiation appears to be one of the most
important factors in the progression of type 2 diabe-
tes 1). Insulin has several functions, including the trans-
port of nutrients into cells, the regulation of gene
expression and energy homeostasis. It acts on a num-
ber of target tissues and through many different intra-
cellular signaling cascades. Elevated levels of intracel-
lular FFAs can blunt the response to insulin and sub-
 Advance Publication
Journal of Atherosclerosis and Thrombosis
Accepted for publication: October 6, 2009
Adipose Tissue and Atherosclerosis 5
published online: February 3, 2010

Fig. 4. Inflammation in adipose tissue induces a vicious cycle.

Enlargement of adipocytes is associated with an increase in the release of FFAs, physical
stress and increased ROS production. These stress factors induce production of inflamma-
tory adipokines such as IL-6, serum amyloid A (SAA) and MCP-1 that are released into
the circulation and mediate the recruitment of activated monocytes into adipose tissue.
The monocytes differentiate into inflammatory macrophages that release TNFα. TNFα
induces further inflammation in the adipocytes and recruitment of macrophages.

sequent metabolic effects 43).

Insulin receptor substrate (IRS)-1 is a key mole-
cule in the insulin signaling pathway, and failure to
activate IRS-1 leads to systemic insulin resistance 44).
Inhibitory phosphorylation of IRS-1 can be induced
through inflammatory agents such as TNFα and IL-6,
but also through activation of receptors such as the
Toll-like receptors (TLR), or intracellular molecules
such as lipids and reactive oxygen species (ROS). Acti-
vation of the TNFα and IL-6 receptors induces activa-
tion of important activators of inflammation i.e. IκB
kinase (IKKβ) and Janus kinase (JNK). JNK is also
activated by FFAs and endoplasmatic reticulum stress,
factors that are associated with obesity-induced activ-
ity. IKKβ does not phosphorylate IRS-1 but causes
insulin resistance through activation of NFκB 45). Sup-
pressor of cytokine signalling (SOCS) inhibits insulins
actions on IRS-1 either by interfering with the tyro-
sine phosphorylation or by targeting IRS-1 for proteo-
somal degradation 44, 46).
The consequences of decreased insulin produc-
tion as a result of ectopic lipid accumulation in the
pancreas combined with a diminished activation of
the insulin receptor in adipocytes results in an impair-
ment of insulin-stimulated glucose transport, a reduced
anti-lipolytic effect, an increase in the amount of FFA
released, impaired preadipocyte differentiation and a
decrease in lipoprotein lipase production and activity.
These effects will lead to the development of insulin
resistance, type 2 diabetes and cardiovascular diseases.
Macrophage Infiltration into Adipose Tissue
There are two kinds of macrophages in adipose
tissue: resident/tissue (or alternatively activated) mac-
rophages and inflammatory macrophages. In severely
obese individuals, the number of macrophages is
higher in visceral fat than subcutaneous fat 47), consis-
tent with a more prominent role for visceral fat in
insulin resistance 48). The infiltration of monocytes/
macrophages into adipocyte tissue is probably initi-
ated by an increase in adipocyte size (Fig. 4). Enlarge-
ment of adipocytes is associated with an increase in
physical stress and ROS production, and increased
secretion of FFA and inflammatory cytokines 2, 49). Of
these cytokines, MCP-1 secreted from macrophages
seems to be the most important 2, 49). MCP-1 is
expressed before inflammatory macrophage mark-
ers 50), providing evidence that cells other than macro-
phages produce it. In obesity, circulating mononuclear
cells are in a proinflammatory state and are key players
in endothelial dysfunction. The transmigration of
blood monocytes into adipose tissue is a complex
mechanism that requires the expression of adherent
molecules both on the monocytes and on the endo-
thelial cells to which they attach 51, 52). After transmi-
gration into adipose tissue, the monocytes differenti-
ate into inflammatory macrophages.
Infiltrating inflammatory macrophages constitute
a major source of inflammatory mediators, especially
TNFα, within adipose tissue, and it is likely that they
 Advance Publication
Journal of Atherosclerosis and Thrombosis
Accepted for publication: October 6, 2009
6 Gustafson
published online: February 3, 2010

Fig. 5. Perivascular adipose tissue and vasocrine signaling.

Increased amounts of perivascular adipose tissue around vessels secrete vasoactive sub-
stances that can both generate local inflammation and alter vascular function. A balance
between the perivascular adipose tissue-derived vasodilator and vasoconstriction factors is
essential for maintaining normal vascular tone. Increased secretion of vasocrine substances
can lead to the increased release of endothelin-1 at the expense of NO and here insulin
has a dual function, modulation of NO synthesis and release of endothelin-1.

act synergistically with adipocytes to amplify local

inflammation 53). Neutralizing antibodies to TNFα
have been shown to inhibit inflammation in a cocul-
ture of 3T3-L1 adipocytes and a macrophage cell line,
suggesting that TNFα is a major macrophage-derived
mediator of inflammation in adipocytes 54). Resident
macrophages have low levels of proinflammatory cyto-
kine production but can be activated with an enhanced
recruitment and activation of blood monocytes 52).
The infiltration of macrophages into adipose tis-
sue contributes to the local and systemic metabolic
effects of obesity, however, the majority of macro-
phages are distributed around necrotic adipocytes
whose numbers increase dramatically in obese individ-
uals. For example, Cinti et al. showed that ＞ 90% of
all macrophages in the adipose tissue of obese individ-
uals were located around dead adipocytes 55). They also
showed a positive correlation between adipocyte death
and adipocyte size and suggested that adipocyte death
helps to mediate local macrophage infiltration 55). It is
proposed that the inflammation in adipocytes entails a
paracrine loop involving FFAs released from adipo-
cytes and TNFα released from macrophages, which,
together with other factors, leads to a further increase
in recruitment of monocytes 54).
Vasocrine Signaling
Excess intake of calories results in increased depo-
sition of perivascular fat around the heart and its major
branches. Conditions where there is an increased
amount of adipose tissue surrounding the blood ves-
sels, overproduction of adipokines, and signaling from
perivascular fat deposits to the arteries, “outside-to-
inside signalling”, could than lead to inflammation
and atherosclerosis (Fig. 5). Perivascular fat is also
considered to be ectopic within adipose tissue, acting
as an integrated organ responsible for both paracrine
signaling and vessel-to-vessel signaling “vasocrine sig-
naling”. Insulin has the rapid effect of increasing
blood flow to skeletal muscle and an ability to recruit
capillaries that depends on its actions to dilate precap-
illary arterioles 56). The most potent inhibitor of insu-
lin’s actions and endothelial nitrogen oxide (NO)-
dependent vasodilation among cytokines is TNFα,
and it is suggested that a high local concentration of
cytokines leads to a blunted activation by insulin of
endothelial NO synthase and increased release of endo-
thelin-1, resulting in a constriction of the arteriole 40).

Adipose Tissue and Atherosclerosis
Fig. 6. Effects of circulating adiponectin.
Adiponectin acts to prevent the deleterious effects of TNFα on endothelial cells by reduc-
ing levels of adhesion molecules and inflammation. Adiponectin also prevents the recruit-
ment of macrophages and formation of foam cells as well as decreases smooth muscle
migration and proliferation.
Effects of Adiponectin
In 1995 and 1996, four different groups inde-
pendently identified adiponectin 57-59). Belonging to
the complement 1q family, adiponectin forms char-
acteristic multimers of which the high molecular
weight (HMW) multimer seems to be the most
important 60, 61). The ratio of the HMW multimer to
other forms is an independent risk factor for meta-
bolic disorders 62). Adiponectin is abundantly expressed
in adipose tissue and circulating levels are high, 5 to
20 μg/mL. Adiponectin levels negatively correlate
with visceral adiposity to a greater extent than with
subcutaneous adiposity.
Kim et al. showed that although overexpression
of adiponectin in ob/ob mice results in normalized
glucose and insulin levels together with improvements
in triglyceride and FFA levels, the mice became
extremely obese due to adipocyte hyperplasia 63).
Despite the obesity, very few macrophages were pres-
ent in adipose tissue, consistent with increased differ-
entiation of new insulin-sensitive adipocytes 63).
Adiponectin and the Vascular System
Adiponectin has effects in a number of different
tissues. For example, in muscle, it counteracts insulin
resistance 64). In arteries, it reduces atherosclerosis and
Advance Publication
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Accepted for publication: October 6, 2009
7
published online: February 3, 2010
intima media thickness 65). It also has effects on capil-
laries and the heart 61). The actions of adiponectin are
summarized in Fig. 6.
Adiponectin attenuates inflammatory actions
at several levels. It reduces TNFα-stimulated expres-
sion of E-selectin, vascular cell adhesion molecule-1
(VCAM-1) and IL-8 in human aortic endothelial
cells 66-68). It also inhibits TNFα-induced activation of
nuclear factor-κB (NFκB) and prevents the prolifera-
tion and migration of smooth muscle cells. Adiponec-
tin inhibits foam cell formation (lipid accumulation in
macrophages) as well as platelet aggregation and T-cell
recruitment and accumulation 69). It has been shown
to inhibit Toll-like receptor-mediated activation of
NFκB in mouse macrophages 70). Adiponectin is also
an important regulator of endothelial NO synthase, a
major determinant of endothelial function and angio-
genesis 71).
Conclusion
Adipose tissue is a central factor in the develop-
ment of insulin resistance and regulation of whole-
body insulin sensitivity. It is also plays an important
role in vascular complications. Adipose tissue has the
ability to modulate both local and systemic processes
in other tissues such as the liver, pancreas, skeletal
muscle, heart and brain. An increase in adipose tissue

8 Gustafson
mass results in the infiltration of macrophages and
enhanced inflammation. Adipokines produced by the
adipose tissue impair insulin signalling and key pro-
teins for glucose uptake. In addition, secreted adipo-
kines promote endothelial dysfunction, adhesion of
monocytes, vascular remodelling and foam cell forma-
tion in the arterial wall, which contribute to cardio-
vascular complications. The reduction in adiponectin
levels with increasing adiposity contributes to obesity-
associated vascular complications.
Acknowledgements
The studies referred to in the authors´ laboratory
were supported by the Swedish Research Council, the
Swedish Diabetes Association, the NovoNordisk
Foundation, the Swedish Foundation for Strategic
Research, the Torsten and Ragnar Soderberg Founda-
tion and the European Union (EUGENE2 LSHM-
CT-2004-512013). The author also thank Rosie Per-
kins for reading and commenting on the manuscript.
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